The goal of this proposal is to secure funds to purchase a multi-tiered proteomic compute (MFC) cluster for University of Washington Health Sciences Center-based principal investigators engaged in biomedical research. The MPC will be located in the School of Pharmacy Mass Spectrometry (SOP MS) facility in the Health Sciences Center, which serves as a fee-for-service operation for UW Pi's wishing to conduct proteomic experiments, and is the only such facility on the UW campus. The SOP MS facility currently has a 10-node compute cluster for processing mass spectrometry-based proteomic experiments, but none for protein folding. The MPC will expand this capability 20-fold. Both traditional hypothesis-driven protein chemistry research and hypothesis-generating research enabled by proteomic techniques will utilize the MPC cluster. All aspects of proteomic and protein chemistry-based research will be supported. For example, we will use it to: 1) fold individual proteins de novo, 2) fold entire proteomes de novo, 3) elucidate protein-protein interactions via chemical cross-linking, 4) map out sub- cellular protein locations, 5) search for multiple anticipated post-translation modifications (PTM's) on individual proteins, 6) search MS-based proteomic data for multiple unsuspected PTM's, and 7) define proteomes. Initially, the MPC cluster will be for support of researchers in the Schools of Pharmacy, Medicine, and Public Health; eventually, however, any PI on campus or from the Seattle region utilizing the SOP MS facility will be given access to the compute power. Initial projects include the following areas of biomedical research: 1) acute respiratory distress syndrome (ARDS) and other lung injury diseases under investigation at the UW- affiliated Harbor view Medical Center, 2) prions and prion folding, 3) Apolipoprotein PTM's, 4) protein-protein cross-linking, 5) vaccine candidates and therapeutic targets in Gram-negative organisms, 6) sub cellular mapping of proteins under conditions of drug-induced liver disease, and 8) toxic-proteomics. [unreadable] [unreadable] [unreadable] [unreadable]